The oxindole skeleton has been recognized as a hetero ring structure commonly found in synthetic compounds in physiologically active natural products and medical applications. In particular, 3-substituted and spirooxindole derivatives have been implicated in a variety of biological activities including serotonin, anti-tumor, anti-alzheimer's, anti-parkinsonian, glycoprotein mediated MDR inhibition, antibacterial and anti-inflammatory activity. The oxindole also acts as a precursor for the synthesis of other heterocyclic compounds, including indoles and isatins. Therefore, the development of a highly efficient new strategy for the synthesis of oxindole structures in organic synthesis has received much attention. With the recent development of direct catalytic C—H functionalization, many studies have been carried out on the synthesis of oxindole via oxidative C—H functionalization without a transition metal catalyst or metal.
In particular, tandem cyclization of acrylamides has attracted attention in the synthesis of various functionalized oxindoles. Another route is the synthesis by Ir or Cu catalyst intramolecular cyclization of β-ketoamide derivatives. In addition, the aromatic C—H functionalization of α-diazoamides by Ag or Rh catalysis is another effective method for synthesizing C3-functionalized oxindoles. However, these processes require essentially starting materials with certain functional groups, which also form subclasses of oxindole.
Recently, azobenzene has been used for catalytic C—H functionalization by using an azo functional group as an aromatic group. In this context, C—H addition and subsequent cyclization reactions are applied for the purpose of constructing various N-heterocyclic molecules.
For example, the synthesis of (2H)-indazoles through catalytic redox neutral coupling of Rh (III), Co (III) or Re (0) with azobenzene and aryl aldehydes is known. In addition, the formation of (2H)-indazole was initiated by Pd (II) catalyzed oxidative acylation and aldehyde reduction cyclization of azobenzene. The cyclization capture approach by Rh (III) catalysts, which synthesize a variety of 1-aminoindoles, is also known.
Also, the synthesis of benzotriazoles in azobenzene and organic azides is also known through amination and cyclization of Rh (III) or Pd (II) catalysis. Recently, the present inventors have demonstrated highly substituted cyanolins derived from azobenzene and α-diazo esters under Rh (III) catalyst (S. Sharma, S H Han, S. Han, W. Ji. J. Oh, S.-Y. Lee, J S Oh, Y H Jung, I S Kim, Org. Lett., 2015, 17, 2852). Other heterocycles, such as cinnoline, 3-acyl-indazole and indole, were also formed by C—H functionalization and cyclization strategies.